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Ethyl Acetate → (S)-3-(tert-butoxycarbonyl)-4-(2-(dimethoxyphosphoryl)-1-oxo-ethyl)-2,2-dimethyloxazolidine

HRID 22084
ノート
印刷プレビュー

反応式

HRID 22084 の反応式
[CH3:1][O:2][P:3]([CH3:7])(=[O:6])[O:4][CH3:5].[Li]CCCC.[C:13]([O:17][C:18]([N:20]1[C@H:24]([C:25]([O-])=[O:26])[CH2:23][O:22][C:21]1([CH3:29])[CH3:28])=[O:19])([CH3:16])([CH3:15])[CH3:14].CCOC(C)=O>C1COCC1.CCO>[C:13]([O:17][C:18]([N:20]1[C@H:24]([C:25](=[O:26])[CH2:7][P:3]([O:4][CH3:5])([O:2][CH3:1])=[O:6])[CH2:23][O:22][C:21]1([CH3:29])[CH3:28])=[O:19])([CH3:16])([CH3:15])[CH3:14]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 12958Dimethyl methylphosphonateHCID 69321863,4-Oxazolidinedicarboxylic acid, 2,2-dimethyl-, 3-(1,1-dimethylethyl) ester, (4S)-HCID 178418339Butyllithium

生成物 1

HCID 11110909(S)-3-(tert-butoxycarbonyl)-4-(2-(dimethoxyphosphoryl)-1-oxo-ethyl)-2,2-dimethyloxazolidine収率 70%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒
HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-75 °C

実験手順

Dimethylmethylphosphonate (2.3 ml, 21 mmol, 210 mol-%) was dissolved in 10 ml of THF and cooled to -85° C. (internal temp. -75° C.). To this solution was added 14 ml (1.6M, 21 mmol, 210 mol-%) of n-BuLi in hexanes. The reaction mixture was allowed to warm to -25° C. for 1 hour and then cooled back to -85° C. (internal temp. <-75° C.) after which 2.6 g (10 mmol, 100 ml-%) of methyl ((S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4oxazolidine carboxylate was dissolved in 5 ml of THF and cooled to -85° C. (internal temperature <-75° C.). This solution was cannulated onto the anion at such a speed that the internal temperature stayed <-75° C. at all times. After the addition the reaction mixture was allowed to warm to 0° C. very slowly and then it was quenched with 5 w-% citric acid. The pH was adjusted to 3 with sat. citric acid and the reaction mixture was extracted several times with ethyl acetate (EtOAc). Organic phases were washed with brine, combined, dried over Na2SO4 and the solvents were removed in vacuo. The product can be crystallized if necessary from iso-octane. An analytical sample was purified by flash chromatography using 20% EtOAc in hexanes to remove the traces of starting material and then as a stepgradient with 100% EtOAc to remove the excess of dimethylmethylphosphonate to yield 70% of pure 3. Rf, 100% EtOAc: 0.28. mp. 86°-7° C. 1H NMR (250 MHz, CDCl3) δ:1.30 (s, 3 H, major rotamer) , 1.36 (s, 3 H, minor rotamer) , 1.40 (s, 3 H both rotamers), 1.51 (s, 3 H, major rotamer), 1.55 (s, 3 H minor rotamer), 3.06 (d, 2 H, major rotamer, 2J(HP)=20 Hz), 3.10 (d, H, minor rotamer, 2H(HP)=20 Hz), 3.68 (d, 6 H, 3J(HP)=11,2 Hz), 3.91 (dd, 1 H, minor rotamer, J=3.6 Hz, <0.5 Hz), 3.93 (dd, 1 H, major rotamer, J=3.6 Hz, <0.5 Hz), 4.05 (m, 1 H, both rotamers) , 4.38 (m, 1 H, major rotamer) , 4.48 (m, 1 H, minor rotamer). Rotameric ratio is 2:1 at 20° C. 13C NMR (50 MHz, CDCl3) δ:23.7 (CH3), 25.0 (CH3), 28.0 (CH3), 52.7 (CH3), 65.0 (c), 65.1 (CH2), 89.8 (c), 94.4 (CH2), 95.(C), 150.9 (C=O), 199.0 (C=O) . Anal. Calcd. C 47.86: H 7.46; N 3.99; Found C 48.11; H 7.70; N 4.26. α20 =-40.1(c=14.0, EtOH).

後処理

  1. temperatureto warm to -25° C. for 1 hour
  2. temperaturecooled to -85° C. (internal temperature <-75° C.)
  3. customstayed <-75° C. at all times
  4. additionAfter the addition the reaction mixture
  5. temperatureto warm to 0° C. very slowly
  6. customit was quenched with 5 w-% citric acid
  7. extractionthe reaction mixture was extracted several times with ethyl acetate (EtOAc)
  8. washOrganic phases were washed with brine
  9. dry with materialdried over Na2SO4
  10. customthe solvents were removed in vacuo
  11. customThe product can be crystallized if necessary from iso-octane
  12. customAn analytical sample was purified by flash chromatography
  13. customto remove the traces of starting material
  14. customas a stepgradient with 100% EtOAc to remove the excess of dimethylmethylphosphonate
  15. customto yield 70% of pure 3
  16. customat 20° C

出典と根拠

ORDレコード
ord-44a1fe8b547741f9b4f4aca0d9506505
出典データセット
uspto-grants-1995_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05426228

反応ノート

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